# Circulating Tumor DNA-Based Assessment of Minimal Residual Disease in Colorectal Cancer: Prognostic and Predictive Implications

## TL;DR

This paper reviews how circulating tumor DNA can detect leftover cancer cells in colorectal cancer patients and guide treatment decisions.

## Contribution

The paper provides a comprehensive review of ctDNA's prognostic and predictive roles in colorectal cancer across treatment stages.

## Key findings

- Post-operative ctDNA positivity is a strong predictor of recurrence in stage II–III colorectal cancer.
- ctDNA monitoring can provide insights into treatment response and resistance in metastatic colorectal cancer.
- Quantitative ctDNA dynamics may refine risk stratification and personalize treatment.

## Abstract

Circulating tumor DNA (ctDNA) is emerging as a promising blood-based biomarker capable of detecting minimal residual disease in patients with colorectal cancer. The presence or absence of ctDNA following surgery or systemic therapy provides valuable information regarding the risk of disease recurrence. In this review, we summarize the current evidence supporting the prognostic and predictive roles of ctDNA across different stages of colorectal cancer and evaluate key completed studies as well as ongoing randomized trials. We also highlight current limitations and future directions for the integration of ctDNA-guided strategies into routine clinical practice.

Circulating tumor DNA (ctDNA) has emerged as a promising and versatile biomarker in colorectal cancer (CRC), providing real-time insights into the tumor burden, minimal residual disease (MRD), and treatment response across both early and metastatic stages. In patients with resected stage II–III CRC, post-operative ctDNA positivity is a robust predictor of recurrence and may outperform traditional clinicopathologic risk factors. It can facilitate adjuvant therapy discussions; however, treatment escalation or de-escalation based solely on ctDNA results is not yet supported by available interventional data. In the metastatic setting, ctDNA-based techniques could provide non-invasive molecular profiling and a monitoring response to systemic therapies. Peripheral blood-based techniques could also help detect emerging resistance to systemic therapy. Emerging evidence highlights that quantitative assessment of ctDNA dynamics, including the baseline burden and post-treatment clearance, could further refine risk stratification and inform treatment personalization. Collectively, ctDNA represents a promising and evolving biomarker with well-established prognostic and emerging predictive potential and is poised to support precision oncology across the continuum of CRC.